Congratulations to the 2019 ALZ Grant Awardees

Intriguing evidence suggests Alzheimer’s disease may have a link to infectious disease or a microbial mechanism. Could this be the missing link to lead to a cure for Alzheimer’s disease? To advance research that could shed light and provide hope to the more than 5.7 Americans and 47 million people worldwide living with the disease, the IDSA Foundation established the Alzheimer’s Research Grant in 2018 to foster further investigation, awarding two research grants. For the endeavor’s second year, the Foundation awarded $500,000 in grants to five researchers who are exploring a potential link between an infectious agent and Alzheimer’s disease.

Chosen from among 47 extremely high-quality applications, the 2019 awardees will each receive a $100,000 grant to pursue their research:

• Maria Eugenia Ariza, PhD, assistant professor at The Ohio State University, Columbus, for her research “Role of the Herpesvirus dUTPase Proteins in Late-Onset Alzheimer’s Disease (LOAD).” There is growing evidence that some herpesviruses play a role in the development of LOAD, but there is a lack of understanding regarding how that occurs. Dr. Ariza and her team have already identified the herpesviruses dUTPases as a new class of proteins that may contribute to the progression of LOAD. This new study will analyze human pluripotent stem cells with different Alzheimer’s disease genes to assess whether a genetic risk factor for LOAD and the dUTPase proteins from herpes simplex virus type 1, Epstein-Barr virus, human herpesvirus 6A and varicella zoster virus work together to cause inflammation in the brain, prompting the production of toxins that lead to the death of neurons. The findings may help in identifying new targets for the development of alternate treatments for LOAD.
• Alberto Costa, MD, PhD, professor at Case Western Reserve University, Cleveland, for his research “Is the Amyloid-Beta Peptide a Necessary Element in Preventing the Spread of Porphyromonas Gingivalis Infection in the Brain?” Costa will assess whether proteins that form amyloid plaques may actually be containing the spread of infection from P. gingivalis, which causes gum disease. He will expose mice with the protein and those without it to P. gingivalis to determine if the infection spreads more quickly or more slowly if the protein that forms amyloid plaques is not there. The results could add to the evidence that oral health plays an important role not only in general health, but also shed more light on whether reducing plaque-causing proteins below a critical level in the brain may actually also have harmful effects.
• Jason Grayson, PhD, associate professor at Wake Forest School of Medicine, Winston-Salem, N.C., for his research “Using Machine Learning to Determine the Role of Herpesvirus-Specific CD8+ T Cells in Alzheimer’s Disease.” While some hypothesize that herpes simplex virus 1 plays a role in Alzheimer’s disease, it is unclear why only some who are infected with that virus develop Alzheimer’s disease. Dr. Grayson will use machine learning to test his hypothesis that Alzheimer’s disease may result from repeated inflammation produced immune system’s CD8+ T cell response to multiple herpes viruses. This knowledge could help lead to therapies that could slow or stop the progression of the disease.
• Catherine Helmer, PhD, permanent researcher at Bordeaux University, France, for her research “Viral Infections in Alzheimer’s disease (VirAlz).” Helmer will test her hypothesis that as the immune system weakens with age and the blood brain barrier becomes leakier, viruses can move to the brain and trigger Alzheimer’s disease. She will assess 13-year data of 1,300 elderly people with repeated assessments of cognition and screening of Alzheimer’s disease and use innovative VirScan technology to determine if there is a history of viral infections during their lives (including infection to herpes simplex virus type 1, herpes human virus 6 and others). The findings could help determine who is at risk and lead to development of preventive therapies.
• Marvin K. Schulte, PhD, professor and department chair at Idaho State University, for his research “Viral Mimicry in Alzheimer’s Disease.” Using a rapid analysis technique called Surface Plasmon Resonance and electrophysiological recordings, Dr. Schulte will test his hypothesis that Alzheimer’s disease may result from a viral infection that leads to the inhibition and degeneration of neural function (and therefore, Alzheimer’s disease). His team will perform experiments to look at potential interactions: of viral proteins with neural receptors; between antibodies to viral proteins and neural receptors; and between antibodies to viral proteins and molecules in the body that regulate the function of neural receptors, such as lymphocyte antigen 6 proteins. This knowledge could help to identify who is at risk of developing Alzheimer’s and lead to preventive therapies.

Further, the 2018 winners report that their grants helped advance their research as follows:

• Colette Cywes-Bentley, PhD, assistant professor of medicine, Brigham & Women’s Hospital, Harvard Medical School was awarded a grant for her project “The Role for Pathogen Expressed PNAG in Alzheimer’s Disease,” which focuses on identifying a link between bacterial exposures and Alzheimer’s disease inflammation characterized by beta-amyloid plaques. She reports that the grant helped her team understand that microbes – or fragments that remain lodged in the brain after infections – may start the process of tissue damage and subsequent disease. “We are on the cusp of performing behavioral studies in mice either vaccinated with a poly-N-acetyl glucosamine (PNAG)-specific or control vaccine to assess whether antibodies induced by the vaccine can prevent beta-amyloid deposits from developing in the mouse brains over time and thereby prevent characteristic behavioral changes in these aged mice.”
• Allison Aiello, PhD, MS, professor and social epidemiology program leader, University of North Carolina, Chapel Hill, was awarded a grant for her project “The Role of Dementia-Associated Pathogen Burden in the Development of Alzheimer’s Disease (AD) and Other Dementias.” The grant allowed them to highlight a significant role for cytomegalovirus in cognitive impairment, and that infection confers up to a 6-point lower score in cognitive function in U.S. adults. They noted that inflammation related cytokines are related to cognitive function and that cortisol has been shown to increase the risk of cognitive impairment. “To our knowledge, this is the first report of an interaction between cortisol and inflammatory markers related to response to infection and cognitive impairment.” The researchers submitted an abstract on their work to two conferences and a manuscript will soon be submitted. The next step is to examine multiple infections and Alzheimer’s disease, as well as the impact of cortisol on infection and the interaction between infection and ApoE on the risk of Alzheimer’s disease.

The IDSA Foundation research grants are designed to:

• Obtain evidence that an infectious agent or microbial community is correlated to Alzheimer’s disease
• Promote novel research in the field of microbial triggers for Alzheimer’s disease

To be eligible for a grant, research must be narrowly focused on identifying the possible role of an infectious agent or agents in causing Alzheimer’s disease. Awards will support innovative research, including basic, clinical and/or non-traditional approaches. Information about the 2020 grants and application information will be available in the coming months. Please check back for updates later this Spring.

Funding for the awards is supported by grants from The Benter Foundation and Alzheimer’s Germ Quest, Inc.